Abstract

The equine-associated obligate pathogen Burkholderia mallei was developed by reductive evolution involving a substantial portion of the genome from Burkholderia pseudomallei, a free-living opportunistic pathogen. With its short history of divergence (∼3.5 myr), B. mallei provides an excellent resource to study the early steps in bacterial genome reductive evolution in the host. By examining 20 genomes of B. mallei and B. pseudomallei, we found that stepwise massive expansion of IS (insertion sequence) elements ISBma1, ISBma2, and IS407A occurred during the evolution of B. mallei. Each element proliferated through the sites where its target selection preference was met. Then, ISBma1 and ISBma2 contributed to the further spread of IS407A by providing secondary insertion sites. This spread increased genomic deletions and rearrangements, which were predominantly mediated by IS407A. There were also nucleotide-level disruptions in a large number of genes. However, no significant signs of erosion were yet noted in these genes. Intriguingly, all these genomic modifications did not seriously alter the gene expression patterns inherited from B. pseudomallei. This efficient and elaborate genomic transition was enabled largely through the formation of the highly flexible IS-blended genome and the guidance by selective forces in the host. The detailed IS intervention, unveiled for the first time in this study, may represent the key component of a general mechanism for early bacterial evolution in the host.

Highlights

  • The genomes of host-adapted bacteria, including endosymbionts and obligatory intracellular pathogens, go through reductive evolution [1,2,3]

  • By comparing genome sequences, we found that three types of IS elements, ISBma1, ISBma2, and IS407A, were significantly increased in B. mallei compared to B. pseudomallei (Fig. 1A)

  • In this study, we unveiled the mechanics of genomic deletions and rearrangements that occur in the early stage of bacterial specialization in the host, by conducting comparative analyses of B. mallei and its parental species, B. pseudomallei

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Summary

Introduction

The genomes of host-adapted bacteria, including endosymbionts and obligatory intracellular pathogens, go through reductive evolution [1,2,3]. During the early stage of the genome reduction process, the majority of genes are lost as large chromosomal fragments spanning multiple genes Such genome reduction has been documented in diverse bacterial groups, including Firmicutes, Chlamydiae, Spirochetes, and c-Proteobacteria [1,3,4,5,6,7]. B. mallei has very recently (,3.5 myr) evolved from a clone of B. pseudomallei through extensive genome reduction [18,19], accounting for as much as 1.41 Mb or 20% of the genome, as estimated by the size difference between the genomes of B. mallei ATCC 23344 and B. pseudomallei K96243 [18,20,21] Concomitant with this process, B. mallei became constantly associated with mammalian hosts, equines [22,23], while B. pseudomallei maintains an opportunistic pathogenic lifestyle [17]. Many of these genes encode metabolic functions for the synthesis of metabolites or the utilization of various sugars and amino acids, without which bacterial propagation in the environment could be significantly hindered [20]

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